Reporter gene-engineering of human induced pluripotent stem cells during differentiation renders in vivo traceable hepatocyte-like cells accessible

Autor: Tamir S Rashid, Marlies C Glatz, Samuel Ji Blackford, Gilbert O. Fruhwirth, Ewelina Kurtys, Candice Ashmore-Harris, Benjamin Grimsdell
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Ashmore-Harris, C, Blackford, S JI, Grimsdell, B, Kurtys, E, Glatz, M, Rashid, T S & Fruhwirth, G O 2019, ' Reporter gene-engineering of human induced pluripotent stem cells during differentiation renders in vivo traceable hepatocyte-like cells accessible ', Stem Cell Research, vol. 41, 101599 . https://doi.org/10.1016/j.scr.2019.101599
Stem Cell Research
Stem Cell Research, Vol 41, Iss, Pp-(2019)
Popis: Highlights • iPSC-derived hepatocyte-like cells (HLCs) rendered traceable in vivo. • Reproducible lentivirus-based gene transfer during the differentiation process. • Protocol and reporter expression did not negatively impact on HLC maturation. • Proof-of-principle shown for whole-body SPECT/CT-afforded HLC in vivo tracking.
Primary hepatocyte transplantation (HTx) is a safe cell therapy for patients with liver disease, but wider application is circumvented by poor cell engraftment due to limitations in hepatocyte quality and transplantation strategies. Hepatocyte-like cells (HLCs) derived from human induced pluripotent stem cells (hiPSC) are considered a promising alternative but also require optimisation of transplantation and are often transplanted prior to full maturation. Whole-body in vivo imaging would be highly beneficial to assess engraftment non-invasively and monitor the transplanted cells in the short and long-term. Here we report a lentiviral transduction approach designed to engineer hiPSC-derived HLCs during differentiation. This strategy resulted in the successful production of sodium iodide symporter (NIS)-expressing HLCs that were functionally characterised, transplanted into mice, and subsequently imaged using radionuclide tomography.
Graphical abstract Image, graphical abstract
Databáze: OpenAIRE